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AMPK inhibitor compound C suppresses cell proliferation by induction of apoptosis and autophagy in human colorectal cancer cells
Author(s) -
Yang WengLang,
Perillo William,
Liou Deanna,
Marambaud Philippe,
Wang Ping
Publication year - 2012
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23184
Subject(s) - ampk , autophagy , apoptosis , cell growth , programmed cell death , autophagosome , survivin , microbiology and biotechnology , viability assay , cancer research , cancer cell , cell culture , protein kinase a , biology , kinase , medicine , cancer , biochemistry , genetics
Background and Objectives AMP‐activated protein kinase (AMPK) is a main regulator of energy metabolism through the inhibition of biosynthetic pathways and enhancement of ATP‐generating pathways. However, targeting AMPK as anti‐tumor therapy remains controversial. In this study, we examined the effect of compound C, a small molecule inhibitor of AMPK, on the proliferation of several human colorectal cancer cell lines with diverse characteristics. Methods Four human colorectal cancer cell lines (HCT116, DLD‐1, SW480, and KM12C) were treated with compound C. Cell viability was determined by MTS assay. Cell cycle prolife was analyzed by flow cytometry. Acidic vesicular organelles were detected by acridine orange staining. Protein levels were measured by western blotting. Results Compound C inhibited the growth of four cell lines in a dose‐dependent manner and caused G 2 /M arrest. Compound C increased sub‐G 1 cell population and induced chromatin condensation and cleavage of PARP in HCT116 and KM12C cells, while it induced acidic vesicular formation and conversion of LC3‐I to autophagosome‐associated LC3‐II in DLD‐1 and SW480 cells. Survivin, an anti‐apoptotic protein, was down‐regulated in all cell lines treated with compound C. Conclusions Compound C induces apoptotic or autophagic death in colorectal cancer cells and the preferred death mode is cell type‐dependent. J. Surg. Oncol. 2012; 106:680–688. © 2012 Wiley Periodicals, Inc.